Auricular Transcutaneous Vagus Nerve Stimulation Specifically Enhances Working Memory Gate Closing Mechanism: A System Neurophysiological Study.

Everyday tasks and goal-directed behavior involve the maintenance and continuous updating of information in working memory (WM). WM gating reflects switches between these two core states. Neurobiological considerations suggest that the catecholaminergic and the GABAergic are likely involved in these dynamics. Both of these neurotransmitter systems likely underlie the effects to auricular transcutaneous vagus nerve stimulation (atVNS). We examine the effects of atVNS on WM gating dynamics and their underlying neurophysiological and neurobiological processes in a randomized crossover study design in healthy humans of both sexes. We show that atVNS specifically modulates WM gate closing and thus specifically modulates neural mechanisms enabling the maintenance of information in WM. WM gate opening processes were not affected. atVNS modulates WM gate closing processes through the modulation of EEG alpha band activity. This was the case for clusters of activity in the EEG signal referring to stimulus information, motor response information, and fractions of information carrying stimulus-response mapping rules during WM gate closing. EEG-beamforming shows that modulations of activity in fronto-polar, orbital, and inferior parietal regions are associated with these effects. The data suggest that these effects are not because of modulations of the catecholaminergic (noradrenaline) system as indicated by lack of modulatory effects in pupil diameter dynamics, in the inter-relation of EEG and pupil diameter dynamics and saliva markers of noradrenaline activity. Considering other findings, it appears that a central effect of atVNS during cognitive processing refers to the stabilization of information in neural circuits, putatively mediated via the GABAergic system.SIGNIFICANCE STATEMENT Goal-directed behavior depends on how well information in short-term memory can be flexibly updated but also on how well it can be shielded from distraction. These two functions were guarded by a working memory gate. We show how an increasingly popular brain stimulation techniques specifically enhances the ability to close the working memory gate to shield information from distraction. We show what physiological and anatomic aspects underlie these effects.

Catecholaminergic Modulation of Metacontrol is Reflected by Changes in Aperiodic EEG Activity.

BACKGROUND: "Metacontrol" describes the ability to maintain an optimal balance between cognitive control styles that are either more persistent or more flexible. Recent studies have shown a link between metacontrol and aperiodic EEG patterns. The present study aimed to gain more insight into the neurobiological underpinnings of metacontrol by using Methylphenidate (MPH), a compound known to increase postsynaptic catecholamine levels and to modulate cortical noise. METHODS: In a double-blind, randomized, placebo-controlled study design, we investigated the effect of methylphenidate (0.5 mg/kg) on aperiodic EEG activity during a flanker task in a sample of n = 25 neurotypical adults. To quantify cortical noise, we employed the FOOOF (fitting oscillations & one over f) algorithm. RESULTS: Compared to placebo, MPH increased the aperiodic exponent, suggesting that it reduces cortical noise in two ways: First, it did so in a state-like fashion, as the main effect of the drug was visible and significant in both pre-trial and within-trial periods. Second, the electrode-specific analyses showed that the drug also affects specific processes by dampening the downregulation of noise in conditions requiring more control. CONCLUSIONS: Our findings suggest that the aperiodic exponent provides a neural marker of metacontrol states and changes therein. Further, we propose that the effectiveness of medications targeting catecholaminergic signaling can be evaluated by studying changes of cortical noise; fostering the idea of using the quantification of cortical noise as an indicator in pharmacological treatment.

The Ability to Voluntarily Regulate Theta Band Activity Affects How Pharmacological Manipulation of the Catecholaminergic System Impacts Cognitive Control.

BACKGROUND: The catecholaminergic system influences response inhibition, but the magnitude of the impact of catecholaminergic manipulation is heterogeneous. Theoretical considerations suggest that the voluntary modulability of theta band activity can explain this variance. The study aimed to investigate to what extent interindividual differences in catecholaminergic effects on response inhibition depend on voluntary theta band activity modulation. METHODS: A total of 67 healthy adults were tested in a randomized, double-blind, cross-over study design. At each appointment, they received a single dose of methylphenidate or placebo and performed a Go/Nogo task with stimuli of varying complexity. Before the first appointment, the individual's ability to modulate theta band activity was measured. Recorded EEG data were analyzed using temporal decomposition and multivariate pattern analysis. RESULTS: Methylphenidate effects and voluntary modulability of theta band activity showed an interactive effect on the false alarm rates of the different Nogo conditions. The multivariate pattern analysis revealed that methylphenidate effects interacted with voluntary modulability of theta band activity at a stimulus processing level, whereas during response selection methylphenidate effects interacted with the complexity of the Nogo condition. CONCLUSIONS: The findings reveal that the individual's theta band modulability affects the responsiveness of an individual's catecholaminergic system to pharmacological modulation. Thus, the impact of pharmacological manipulation of the catecholaminergic system on cognitive control most likely depends on the existing ability to self-modulate relevant brain oscillatory patterns underlying the cognitive processes being targeted by pharmacological modulations.

Interindividual aperiodic resting-state EEG activity predicts cognitive-control styles.

The ability to find the right balance between more persistent and more flexible cognitive-control styles is known as "metacontrol." Recent findings suggest a relevance of aperiodic EEG activity and task conditions that are likely to elicit a specific metacontrol style. Here we investigated whether individual differences in aperiodic EEG activity obtained off-task (during resting state) predict individual cognitive-control styles under task conditions that pose different demands on metacontrol. We analyzed EEG resting-state data, task-EEG, and behavioral outcomes from a sample of N = 65 healthy participants performing a Go/Nogo task. We examined aperiodic activity as indicator of "neural noise" in the EEG power spectrum, and participants were assigned to a high-noise or low-noise group according to a median split of the exponents obtained for resting state. We found that off-task aperiodic exponents predicted different cognitive-control styles in Go and Nogo conditions: Overall, aperiodic exponents were higher (i.e., noise was lower) in the low-noise group, who however showed no difference between Go and Nogo trials, whereas the high-noise group exhibited significant noise reduction in the more persistence-heavy Nogo condition. This suggests that trait-like biases determine the default cognitive-control style, which however can be overwritten or compensated for under challenging task demands. We suggest that aperiodic activity in EEG signals represents valid indicators of highly dynamic arbitration between metacontrol styles, representing the brain's capability to reorganize itself and adapt its neural activity patterns to changing environmental conditions.

Aperiodic neural activity reflects metacontrol.

Higher-level cognitive functions are mediated via complex oscillatory activity patterns and its analysis is dominating cognitive neuroscience research. However, besides oscillatory (period) activity, also aperiodic activity constitutes neural dynamics, but its relevance for higher-level cognitive functions is only beginning to be understood. The present study examined whether the broadband EEG aperiodic activity reflects principles of metacontrol. Metacontrol conceptualizes whether it is more useful to engage in more flexible processing of incoming information or to shield cognitive processes from incoming information (persistence-heavy processing). We examined EEG and behavioral data from a sample of n = 191 healthy participants performing a Simon Go/NoGo task that can be assumed to induce different metacontrol states (persistence-biased vs. flexibility-biased). Aperiodic activity was estimated using the FOOOF toolbox in the EEG power spectrum. There was a higher aperiodic exponent and offset in NoGo trials compared with Go trials, in incongruent (Go) trials compared with congruent (Go) trials. Thus, aperiodic activity increases during persistence-heavy processing, but decreases during flexibility-heavy processing. These findings link aperiodic features of the EEG signal and concepts describing the dynamics of how cognitive control modes are applied. Therefore, the study substantially extends the importance of aperiodic activity in understanding cognitive functions.

Evidence for independent representational contents in inhibitory control subprocesses associated with frontoparietal cortices.

Inhibitory control processes have intensively been studied in cognitive science for the past decades. Even though the neural dynamics underlying these processes are increasingly better understood, a critical open question is how the representational dynamics of the inhibitory control processes are modulated when engaging in response inhibition in a relatively automatic or a controlled mode. Against the background of an overarching theory of perception-action integration, we combine temporal and spatial EEG signal decomposition methods with multivariate pattern analysis and source localization to obtain fine-grained insights into the neural dynamics of the representational content of response inhibition. For this purpose, we used a sample of N = 40 healthy adult participants. The behavioural data suggest that response inhibition was better in a more controlled than a more automated response execution mode. Regarding neural dynamics, effects of response inhibition modes relied on a concomitant coding of stimulus-related information and rules of how stimulus information is related to the appropriate motor programme. Crucially, these fractions of information, which are encoded at the same time in the neurophysiological signal, are based on two independent spatial neurophysiological activity patterns, also showing differences in the temporal stability of the representational content. Source localizations revealed that the precuneus and inferior parietal cortex regions are more relevant than prefrontal areas for the representation of stimulus-response selection codes. We provide a blueprint how a concatenation of EEG signal analysis methods, capturing distinct aspects of neural dynamics, can be connected to cognitive science theory on the importance of representations in action control.

Alpha and theta band activity share information relevant to proactive and reactive control during conflict-modulated response inhibition.

Response inhibition is an important instance of cognitive control and can be complicated by perceptual conflict. The neurophysiological mechanisms underlying these processes are still not understood. Especially the relationship between neural processes directly preceding cognitive control (proactive control) and processes underlying cognitive control (reactive control) has not been examined although there should be close links. In the current study, we investigate these aspects in a sample of N = 50 healthy adults. Time-frequency and beamforming approaches were applied to analyze the interrelation of brain states before (pre-trial) and during (within-trial) cognitive control. The behavioral data replicate a perceptual conflict-dependent modulation of response inhibition. During the pre-trial period, insular, inferior frontal, superior temporal, and precentral alpha activity was positively correlated with theta activity in the same regions and the superior frontal gyrus. Additionally, participants with a stronger pre-trial alpha activity in the primary motor cortex showed a stronger (within-trial) conflict effect in the theta band in the primary motor cortex. This theta conflict effect was further related to a stronger theta conflict effect in the midcingulate cortex until the end of the trial. The temporal cascade of these processes suggests that successful proactive preparation (anticipatory information gating) entails a stronger reactive processing of the conflicting stimulus information likely resulting in a realization of the need to adapt the current action plan. The results indicate that theta and alpha band activity share and transfer aspects of information when it comes to the interrelationship between proactive and reactive control during conflict-modulated motor inhibition.

Alpha and Theta Bands Dynamics Serve Distinct Functions during Perception-Action Integration in Response Inhibition.

The ability to inhibit responses is central for situational behavior. However, the mechanisms how sensory information is used to inform inhibitory control processes are incompletely understood. In the current study, we examined neurophysiological processes of perception-action integration in response inhibition using the theory of event coding as a conceptual framework. Based on theoretical considerations, we focused on theta and alpha band activity in close connection to the functional neuroanatomical level using EEG beamforming. Moreover, we performed a network-based analysis of theta and alpha band activity. We show a seesaw-like relationship between medial and superior frontal cortex theta band activity and frontoparietal cortex alpha band activity during perception-action integration in response inhibition, depending on the necessity to reconfigure perception-action associations. When perception-action integration was more demanding, because perception-action associations (bindings) have to be reconfigured, there was an increase of theta and a decrease of alpha band activity. Vice versa, when there was no need to reconfigure perception-action bindings, theta band activity was low and alpha band activity was high. However, theta band processes seem to be most important for perception-action integration in response inhibition, because only the sensor-level network organization of theta band activity showed variations depending on the necessity to reconfigure perception-action associations. When no reconfiguration was necessary, the network architecture was more small-world-like, likely enabling efficient processing. When reconfigurations were necessary, the network organization becomes more random. These differences were particularly strong for fractions of the neurophysiological signal supposed to reflect response selection processes.

Processing of embedded response plans is modulated by an interplay of frontoparietal theta and beta activity.

Even simple actions like opening a door require integration/binding and flexible reactivation of different motor elements. Yet, the neural mechanisms underlying the processing of such "embedded response plans" are largely elusive, despite theoretical frameworks, such as the theory of event coding, describing the involved cognitive processes. In a sample of n = 40 healthy participants, we combine time-frequency decomposition and various beamforming methods to examine the neurophysiological dynamics of such action plans, with special emphasis on the interplay of theta and beta frequency activity during the processing of these plans. We show that the integration and rule-guided reactivation of embedded response plans is modulated by a complex interplay of theta and beta activity. Pretrial beta-band activity (BBA) is related to different functional neuroanatomical structures that are activated in a consecutive fashion. Enhanced preparatory activity is positively associated with higher binding-related BBA in the precuneus/parietal areas, indicating that activity in the precuneus/parietal cortex facilitates the execution of an embedded action sequence. Increased preparation subsequently leads to reduced working memory retrieval demands. A cascading pattern of interactions between pretrial and within-trial activity indicates the importance of preparatory brain activity. The study shows that there are multiple roles of beta and theta oscillations associated with different functional neuroanatomical structures during the integration and reactivation of motor elements during actions.NEW & NOTEWORTHY Even simple actions like opening a door require integration/binding and flexible reactivation of different motor elements. Yet, the neural mechanisms underlying the processing of such "embedded response plans" are largely elusive. The study shows that there are multiple roles of beta and theta oscillations associated with different functional neuroanatomical structures during the integration and reactivation of motor elements during actions.

Auricular Transcutaneous Vagus Nerve Stimulation Diminishes Alpha-Band-Related Inhibitory Gating Processes During Conflict Monitoring in Frontal Cortices.

BACKGROUND: Pursuing goals is compromised when being confronted with interfering information. In such situations, conflict monitoring is important. Theoretical considerations on the neurobiology of response selection and control suggest that auricular transcutaneous vagus nerve stimulation (atVNS) should modulate conflict monitoring. However, the neurophysiological-functional neuroanatomical underpinnings are still not understood. METHODS: AtVNS was applied in a randomized crossover study design (n = 45). During atVNS or sham stimulation, conflict monitoring was assessed using a Flanker task. EEG data were recorded and analyzed with focus on theta and alpha band activity. Beamforming was applied to examine functional neuroanatomical correlates of atVNS-induced EEG modulations. Moreover, temporal EEG signal decomposition was applied to examine different coding levels in alpha and theta band activity. RESULTS: AtVNS compromised conflict monitoring processes when it was applied at the second appointment in the crossover study design. On a neurophysiological level, atVNS exerted specific effects because only alpha-band activity was modulated. Alpha-band activity was lower in middle and superior prefrontal regions during atVNS stimulation and thus lower when there was also a decline in task performance. The same direction of alpha-band modulations was evident in fractions of the alpha-band activity coding stimulus-related processes, stimulus-response translation processes, and motor response-related processes. CONCLUSIONS: The combination of prior task experience and atVNS compromises conflict monitoring processes. This is likely due to reduction of the alpha-band-associated inhibitory gating process on interfering information in frontal cortices. Future research should pay considerable attention to boundary conditions affecting the direction of atVNS effects.

Event-related synchronization/desynchronization and functional neuroanatomical regions associated with fatigue effects on cognitive flexibility.

Cognitive flexibility is an essential prerequisite for goal-directed behavior, and daily observations already show that it deteriorates when one is engaged in a task for a (too) long time. Yet, the neural mechanisms underlying such fatigability effect in cognitive flexibility are poorly understood. We examined how theta, alpha, and beta frequency event-related synchronization and desynchronization processes during cued memory-based task switching are modulated by time-on-task effects. We put special emphasis on the examination of functional neuroanatomical regions being associated with these modulations, using EEG beamforming. We show clear declines in task switching performance (increased switch costs) with time on task. For processes occurring before rule switching or repetition processes, we show that anticipatory attentional sampling and selection mechanisms associated with fronto-parietal structures are modulated by time-on-task effects but sensory areas (occipital cortex) also show fatigability-dependent modulations. After target stimulus presentation, the allocation of processing resources for response selection as reflected by theta-related activity in parietal cortices is compromised with time on task and similarly a concomitant increase in alpha and beta band-related attentional processing or gating mechanisms in frontal and occipital regions. Yet, considering the behavioral data showing an apparent decline in performance, this probably compensatory increase is still insufficient to allow reasonable performance. The same is likely the case for processes occurring before rule switching or repetition processes. Comparative analyses show that modulations of alpha band activity are as strongly modulated by fatigability as theta band activity. Implications of these findings for theoretical concepts on fatigability are discussed.NEW & NOTEWORTHY We examine the neurophysiological and functional neuroanatomical basis of fatigability in cognitive flexibility. We show that alpha and theta modulations in fronto-parietal and primary sensory areas are central for the understanding of fatigability effects in cognitive flexibility.

Neural dynamics of stimulus-response representations during inhibitory control.

The investigation of action control processes is one major field in cognitive neuroscience and several theoretical frameworks have been proposed. One established framework is the "Theory of Event Coding" (TEC). However, only rarely, this framework has been used in the context of response inhibition and how stimulus-response association or binding processes modulate response inhibition performance. Particularly the neural dynamics of stimulus-response representations during inhibitory control are elusive. To address this, we examined n = 40 healthy controls and combined temporal EEG signal decomposition with source localization and temporal generalization multivariate pattern analysis (MVPA). We show that overlaps in features of stimuli used to trigger either response execution or inhibition compromised task performance. According to TEC, this indicates that binding processes in event file representations impact response inhibition through partial repetition costs. In the EEG data, reconfiguration of event files modulated processes in time windows well-known to reflect distinct response inhibition mechanisms. Crucially, event file coding processes were only evident in a specific fraction of neurophysiological activity associated with the inferior parietal cortex (BA40). Within that specific fraction of neurophysiological activity, the decoding of the dynamics of event file representations using temporal generalization MVPA suggested that event file representations are stable across several hundred milliseconds, and that event file coding during inhibitory control is reflected by a sustained activation pattern of neural dynamics.NEW & NOTEWORTHY The "mental representation" of how stimulus input translate into the appropriate response is central for goal-directed behavior. However, little is known about the dynamics of such representations on the neurophysiological level when it comes to the inhibition of motor processes. This dynamic is shown in the current study.

The interplay of resting and inhibitory control-related theta-band activity depends on age.

Resting-state neural activity plays an important role for cognitive control processes. Regarding response inhibition processes, an important facet of cognitive control, especially theta-band activity has been the focus of research. Theoretical considerations suggest that the interrelation of resting and task-related theta activity is subject to maturational effects. To investigate whether the relationship between resting theta activity and task-related theta activity during a response inhibition task changes even in young age, we tested N = 166 healthy participants between 8 and 30 years of age. We found significant correlations between resting and inhibitory control-related theta activity as well as behavioral inhibition performance. Importantly, these correlations were moderated by age. The moderation analysis revealed that higher resting theta activity was associated with stronger inhibition-related theta activity in individuals above the age of ~10.7 years. The EEG beamforming analysis showed that this activity is associated with superior frontal region function (BA6). The correlation between resting and superior frontal response inhibition-related theta activity became stronger with increasing age. A similar pattern was found for response inhibition performance, albeit only evident from the age of ~19.5 years. The results suggest that with increasing age, resting theta activity becomes increasingly important for processing the alarm/surprise signals in superior frontal brain regions during inhibitory control. Possible causes for these developmental changes are discussed.

Perception-Action Integration Is Modulated by the Catecholaminergic System Depending on Learning Experience.

BACKGROUND: The process underlying the integration of perception and action is a focal topic in neuroscientific research and cognitive frameworks such as the theory of event coding have been developed to explain the mechanisms of perception-action integration. The neurobiological underpinnings are poorly understood. While it has been suggested that the catecholaminergic system may play a role, there are opposing predictions regarding the effects of catecholamines on perception-action integration. METHODS: Methylphenidate (MPH) is a compound commonly used to modulate the catecholaminergic system. In a double-blind, randomized crossover study design, we examined the effect of MPH (0.25 mg/kg) on perception-action integration using an established "event file coding" paradigm in a group of n = 45 healthy young adults. RESULTS: The data reveal that, compared with the placebo, MPH attenuates binding effects based on the established associations between stimuli and responses, provided participants are already familiar with the task. However, without prior task experience, MPH did not modulate performance compared with the placebo. CONCLUSIONS: Catecholamines and learning experience interactively modulate perception-action integration, especially when perception-action associations have to be reconfigured. The data suggest there is a gain control-based mechanism underlying the interactive effects of learning/task experience and catecholaminergic activity during perception-action integration.

A novel approach to intra-individual performance variability in ADHD.

Patients with attention deficit/(hyperactivity) disorder (AD(H)D) show increased intra-individual variability (IIV) in behavioral performance. This likely reflects dopaminergic deficiencies. However, the precise performance profile across time and the pattern of fluctuations within it have not yet been considered, partly due to insufficient methods. Yet, such an analysis may yield important theory-based implications for clinical practice. Thus, in a case-control cross-sectional study, we introduce a new method to investigate performance fluctuations in patients with ADD (n = 76) and ADHD (n = 67) compared to healthy controls (n = 45) in a time estimation task. In addition, we also evaluate the effects of methylphenidate (MPH) treatment on this performance pattern in 29 patients with AD(H)D. Trial-by-trial differences in performance between healthy controls and patients with AD(H)D do not persist continuously over longer time periods. Periods during which no differences in performance between healthy controls and patients occur alternate with periods in which such differences are present. AD(H)D subtype and surprisingly also medication status does not affect this pattern. The presented findings likely reflect (phasic) deficiencies of the dopaminergic system in patients with AD(H)D which are not sufficiently ameliorated by first-line pharmacological treatment. The presented findings carry important clinical and scientific implications.

Connecting EEG signal decomposition and response selection processes using the theory of event coding framework.

The neurophysiological mechanisms underlying the integration of perception and action are an important topic in cognitive neuroscience. Yet, connections between neurophysiology and cognitive theoretical frameworks have rarely been established. The theory of event coding (TEC) details how perceptions and actions are associated (bound) in a common representational domain (the "event file"), but the neurophysiological mechanisms underlying these processes are hardly understood. We used complementary neurophysiological methods to examine the neurophysiology of event file processing (i.e., event-related potentials [ERPs], temporal EEG signal decomposition, EEG source localization, time-frequency decomposition, EEG network analysis). We show that the P3 ERP component and activity modulations in inferior parietal regions (BA40) reflect event file binding processes. The relevance of this parietal region is corroborated by source localization of temporally decomposed EEG data. We also show that temporal EEG signal decomposition reveals a pattern of results suggesting that event file processes can be dissociated from pure stimulus and response-related processes in the EEG signal. Importantly, it is also documented that event file binding processes are reflected by modulations in the network architecture of theta frequency band activity. That is, when stimulus-response bindings in event files hamper response selection this was associated with a less efficient theta network organization. A more efficient organization was evident when stimulus-response binding in event files facilitated response selection. Small-world network measures seem to reflect event file processing. The results show how cognitive-theoretical assumptions of TEC can directly be mapped to the neurophysiology of response selection.

Resting theta activity is associated with specific coding levels in event-related theta activity during conflict monitoring.

Brain electrical activity in the theta frequency band is essential for cognitive control (e.g., during conflict monitoring), but is also evident in the resting state. The link between resting state theta activity and its relevance for theta-related neural mechanisms during cognitive control is still undetermined. Yet, theoretical considerations suggest that there may be a connection. To examine the link between resting state theta activity and conflict-related theta activity, we combined temporal EEG signal decomposition methods with time-frequency decomposition and beamforming methods in N = 86 healthy participants. Results indicate that resting state theta activity is closely associated with the strength of conflict-related neural activity at the level of ERPs and total theta power (consisting of phase-locked and nonphase-locked aspects of theta activity). The data reveal that resting state theta activity is related to a specific aspect of conflict-related theta activity, mainly in superior frontal regions and in the supplemental motor area (SMA, BA6) in particular. The signal decomposition showed that only stimulus-related, but not motor-response-related coding levels in the EEG signal and the event-related total theta activity were associated with resting theta activity. This specificity of effects may explain why the association between resting state theta activity and overt conflict monitoring performance may not be as strong as often assumed. The results suggest that resting state theta activity is particularly important to consider for input integration processes during cognitive control.

Learning Experience Reverses Catecholaminergic Effects on Adaptive Behavior.

BACKGROUND: Catecholamines are important for cognitive control and the ability to adapt behavior (e.g., after response errors). A prominent drug that modulates the catecholaminergic system is methylphenidate. On the basis of theoretical consideration, we propose that the effects of methylphenidate on behavioral adaptation depend on prior learning experience. METHODS: In a double-blind, randomized, placebo-controlled crossover study design, we examined the effect of methylphenidate (0.25 mg/kg) on post error behavioral adaptation processes in a group of n = 43 healthy young adults. Behavioral adaptation processes were examined in a working memory, modulated response selection task. The focus of the analysis was on order effects within the crossover study design to evaluate effects of prior learning/task experience. RESULTS: The effect of methylphenidate/placebo on post-error behavioral adaptation processes reverses depending on prior task experience. When there was no prior experience with the task, methylphenidate increased post-error slowing and thus intensified behavioral adaptation processes. However, when there was prior task experience, (i.e., when the placebo session was conducted first in the crossover design), methylphenidate even decreased post-error slowing and behavioral adaptation. Effect sizes were large and the power of the observed effects was higher than 95%. CONCLUSIONS: The data suggest that catecholaminergic effects on cognitive control functions vary as a function of prior learning/task experience. The data establish a close link between learning/task familiarization and catecholaminergic effects for executive functions, which has not yet been studied, to our knowledge, but is of considerable clinical relevance. Theoretical implications are discussed.

High-dose ethanol intoxication decreases 1/f neural noise or scale-free neural activity in the resting state.

Binge drinking is a frequent phenomenon in many western societies and has been associated with an increased risk of developing alcohol use disorder later in life. Yet, the effects of high-dose alcohol intoxication on neurophysiological processes are still quite poorly understood. This is particularly the case given that neurophysiological brain activity not only contains recurring (oscillatory) patterns of activity, but also a significant fraction of "scale-free" or arrhythmic dynamics referred to as 1/f type activity, pink noise, or 1/f neural noise. Neurobiological considerations suggest that it should be modulated by alcohol intoxication. To investigate this assumption, we collected resting state EEG data from n = 23 healthy young male subjects in a crossover design, where each subject was once tested sober and once tested while intoxicated (mean breath alcohol concentration of 1.1 permille ±0.2). Analyses of the 1/f neural dynamics showed that ethanol intoxication decreased resting state 1/f neural noise, as compared with a sober state. The effects were strongest when the eyes were closed and particularly reliable in the beta frequency band. Given that the dynamics of the beta band have been shown to strongly depend on GABAA receptor neural transmission, this finding nicely aligns with the fact that ethanol increases GABAergic signaling. The study reveals a currently unreported effect of binge drinking on neurophysiological dynamics, which likely revealed a higher sensitivity for ethanol effects than most commonly considered measures of power in neural oscillations. Implications and applicability of these findings are discussed.

On the interrelation of 1/f neural noise and norepinephrine system activity during motor response inhibition.

Several lines of evidence suggest that there is a close interrelation between the degree of noise in neural circuits and the activity of the norepinephrine (NE) system, yet the precise nexus between these aspects is far from being understood during human information processing and cognitive control in particular. We examine this nexus during response inhibition in n = 47 healthy participants. Using high-density EEG recordings, we estimate neural noise by calculating "1/f noise" of those data and integrate these EEG parameters with pupil diameter data as an established indirect index of NE system activity. We show that neural noise is reduced when cognitive control processes to inhibit a prepotent/automated response are exerted. These neural noise variations were confined to the theta frequency band, which has also been shown to play a central role during response inhibition and cognitive control. There were strong positive correlations between the 1/f neural noise parameter and the pupil diameter data within the first 250 ms after the Nogo stimulus presentation at centro-parietal electrode sites. No such correlations were evident during automated responding on Go trials. Source localization analyses using standardized low-resolution brain electromagnetic tomography show that inferior parietal areas are activated in this time period in Nogo trials. The data suggest an interrelation of NE system activity and neural noise within early stages of information processing associated with inferior parietal areas when cognitive control processes are required. The data provide the first direct evidence for the nexus between NE system activity and the modulation of neural noise during inhibitory control in humans. NEW & NOTEWORTHY This is the first study showing that there is a nexus between norepinephrine system activity and the modulation of neural noise or scale-free neural activity during inhibitory control in humans. It does so by integrating pupil diameter data with analysis of EEG neural noise.